Supplemental materials for:

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1 Supplemental materials for: Maciosek MV, LaFrance A, Dehmer SP, McGree D, Flottemesch TJ, Xu Z, Solberg LI. Updated priorities among effective clinical preventive services. Ann Fam Med. 2017;15(1): Page 1 of 8

2 Appendix Scope of preventive services The clinical preventive services considered for this update included A and B grade recommended services of the USPSTF for the general population and for those at increased risk for cardiovascular disease (CVD) or sexually transmitted infections (STIs), as well as ACIP recommendations for the general population. Services for the general population include evidence-based primary and secondary clinical preventive services for which the recommended population is limited only by age or sex criteria. The services recommended for those at increased risk for CVD or STIs were included because those populations are generally large enough to be included in an evaluation of services for the general population and are important at-risk populations for providers, health systems, employers and public health agencies. Services that are routinely co-occurring, such as childhood vaccines, were evaluated as one service. Two groups of services were evaluated as one because they are typically delivered together. The childhood immunization series is delivered with multiple vaccinations in a single visit, and vaccine administration costs are lower for any subsequent vaccines provided in a visit. In addition, new combination vaccines such as the combined measles, mumps, rubella (MMR) and varicella vaccine take advantage of evidence-based vaccination timing to reduce the number of shots and vaccine administration costs. Similarly, the USPSTF now recommends chlamydia and gonorrhea as a single service. These s have the same recommended populations, and the services would be provided simultaneously. Four recommended services that meet those criteria could not be included during the timeline for this update. They are: fluoride varnish, intimate partner violence, STD prevention counseling, and for abnormal blood glucose in overweight and obese. In addition, our estimate for the HPV vaccine includes only females at this time. We intend to analyze and include these services with incremental updates to the ranking as discussed below. We excluded preventive services receiving C, D, and I grades from the USPSTF, services recommended by the USPSTF for newborns and delivered in hospital settings, and services recommended for pregnant women and delivered during prenatal care visits. USPSTF recommendations for high-risk groups other than those at increased risk for CVD or STIs also were not included, such as risk factor for women who have family members with breast, ovarian, tubal, or peritoneal cancer history. Catch-up vaccinations and vaccinations recommended by ACIP for higher-risk populations including health care workers and travelers were excluded to focus on services for the general population. Important influences on estimates Close attention to the specifics of the USPSTF or ACIP recommendation, knowledge of the evidence base and an understanding of the limitations of the model for each service are necessary to fully understand the ranking. We provide reports for quantitative estimates of CPB and CE for services online. However, Table A1 provides some of the most important considerations for each service for those who wish to more quickly obtain a better understanding of the ranking or the scores of a particular service. Rankings over time Page 2 of 8

3 Table A2 highlights changes in total scores since the previous rankings in 2001 and 2006 for services in the current ranking. Services declared inactive since the previous ranking were excluded. In cases where total scores change by two points over time, there was a significant change to either the recommended population, the evidence available for modeling or the underlying burden of disease. Only two services had a change of score of more than two since the 2006 ranking. Counseling on healthy diet for those at increased risk for CVD had significant changes in both the recommended population and the evidence available for modeling. The introduction of the youth pneumococcal conjugate vaccine (PCV13) into the routine childhood immunization schedule substantially reduced the burden of disease among older adults. Then, in 2014, ACIP added the PCV13 vaccine to the prior recommendation of 23- valent pneumococcal polysaccharide vaccine for older adults. Even though the addition of PCV13 was shown to be cost-effective, 47 it reduced the overall cost-effectiveness of this service. Counseling to discourage tobacco initiation is once again in the ranking based on an updated evidence review, and receives the highest possible total score of 10. The service was included in the 2001 ranking based on the USPSTF s prior grading method, which gave it an A grade for evidence that changing behavior would improve health and a C for insufficient evidence that clinician counseling reduced tobacco initiation. It received a total score of 8 in 2001 using conservative assumptions of counseling effectiveness. The recommendation was retired when the USPTF revised its evidence grading methods. Since then, new studies have shown that brief counseling for youth can reduce the probability of initiation by about 20% 48 (about 2 percentage points) and our microsimulation model indicates that counseling youth will produce substantial health benefits and cost-savings over the long-term. Some services had significant changes without affecting scores. For example, starting with the 2006 ranking, we interpreted the USPSTF recommendation for breast cancer to include women ages 40-49, who elect to be screened following a shared decision-making process with a provider. This increased the estimate of CPB and decreased the estimate of cost-effectiveness without changing the total score of six. In the current ranking, breast cancer receives a five. That change is primarily due to the addition of other services and changes to the estimates of previously recommended services. Table A1. Services and Considerations on Estimations and Scoring Services (short Changes and other factors that affect estimation Description name) and scoring Childhood immunization series Tobacco use, brief prevention ACIP childhood immunization series. Estimate includes all recommended vaccines up to 10 years of age (Diphtheria, tetanus, pertussis; measles, mumps, rubella; inactivated polio virus; Haemophilus influenzae type b; Hepatitis A; Hepatitis B; varicella; pneumococcal conjugate; influenza; and rotavirus) plus influenza vaccination to age 18. Provide interventions to prevent initiation, Combined into a single series because multiple vaccines are frequently delivered in a single visit and well-child care visits are often organized around the vaccine schedule. In estimating cost of the series, we took into account savings from providing multiple vaccines in a single visit and using newer combined vaccines that reduce vaccine administration costs. If estimated separately, each individual series of vaccinations would not fare as well as the overall series. Estimated benefits are based on smoking-attributable diseases that don't develop during adult years when CPB CE Total Score Page 3 of 8

4 counseling, youth Tobacco use and brief counseling, adults Alcohol misuse and brief intervention Aspirin chemoprevention for those at higher risk of CVD Cervical cancer Colorectal cancer Chlamydia and gonorrhea Cholesterol Hypertension including education or brief counseling. Screen adults for tobacco use and provide brief cessation counseling and pharmacotherapy. Screen adults misuse and provide brief counseling to reduce alcohol use. Low-dose aspirin use for primary prevention of CVD in adults ages with 10% or greater 10- year CVD risk and other factors. Screen for cervical cancer in women ages 21 to 65 with cytology (Pap smear) every three years. Screen adults years routinely. Screen for chlamydia and gonorrhea in sexually active women ages 24 and younger, and in older women at increased risk for infection. Screen routinely for lipid disorders for men aged 35+, and younger men and women of all ages who are at increased risk of CHD. Treat with lipidlowering medications. Measure blood pressure routinely in all adults and treat with antihypertensive medication to prevent the incidence of CVD. prevented initiation avoids years of increased risk of living as a current or former smoker. New evidence indicates a larger impact of brief counseling on youth initiation than used in estimates for the 2001 ranking. Benefits reflect the health improvement from smokers becoming a former smoker at an earlier age than they would without brief intervention. Estimated benefits are from brief intervention (not from multiplecounseling cessation), but do reflect repeated brief intervention for as many years as an individual remains a smoker. Estimates reflect the impact of only brief intervention in reducing risky drinking such as binge drinking. They reflect neither the costs nor the benefits of treating alcohol dependence. Estimated benefits reflect repeated brief interventions over a lifetime. Financial benefits include substantial reductions in non-medical direct costs, such as from prevented automobile and other property damage. The CE ratio is relatively unstable because costs and financial benefits are nearly equal and are large relative to the QALYs saved; therefore in sensitivity analysis, changes to model inputs that affect net costs create large changes in the CE ratio. Reflects the new provisional recommendation of the USPSTF. The new recommendation is more targeted, which results in greater savings per person but lower population health impact when compared to our prior estimates for this service. Estimates reflect the fact that the HPV vaccine was not available to the age group at greatest risk for cervical cancer at the time they were adolescents. Estimates reflect a mix of endoscopy and FOBT testing. The increased uncertainty of the total score reflects possibility of both CPB and CE score being reduced by 1 in sensitivity analysis. Chlamydia was estimated by itself in prior rankings. The USPSTF now recommends chlamydia and gonorrhea as a combined service, with both s to be provided to the same population. Uncertainty on the health-related quality-of-life effects of infertility increases the uncertainty of scores. Compared to the recommendation used in our prior analysis, the updated USPSTF recommendation calls for more targeted in women a a a AAA Screen men ages Higher uncertainty of total score reflects potential for a Page 4 of 8

5 Healthy diet and physical activity counseling for those at higher risk of CVD HIV HPV immunization Influenza immunization, adults Obesity, adults Syphilis who have ever smoked one time for abdominal aortic aneurysm, using ultrasonography. Offer or refer adults who are overweight or obese with additional CVD risk factors to intensive behavioral counseling to promote healthful diet and physical activity. Screen for HIV infection in adolescents and adults aged 15 to 65 years. Frequency varies by risk level. Administer a 3-dose series of HPV vaccine to all females aged years. Immunize all adults against influenza annually. Screen all adults routinely for obesity. Refer patients with a BMI of 30 kg/m2 or higher to intensive behavioral interventions. Screen all persons at increased risk for syphilis infection. CE score to fall by 2 in sensitivity analysis due to dense distribution of CE estimates among many services in the is range. Compared to its prior recommendation, the USPSTF's updated recommendation is for a more targeted population of overweight or obese people with at least one other CVD risk factor. Costs include a substantial time cost for patients to participate in intensive intervention and out-of-pocket costs for physical activity and improved diet. Therefore, the service would be more cost-effective from a medical payer's perspective that excludes these costs. Impact now includes direct impact on blood pressure, cholesterol and diabetes risk. In prior estimates, impact was limited to health improvements obtained though BMI reduction. Estimates are based on one-time for the general population and annul for those at increased risk for HIV. The increased uncertainty of total score reflects potential for CE score to fall by 2 due to dense distribution of CE estimates among many services in the range and also reflects greater uncertainty related to deriving estimates that are consistent with those for other services in this list from a published study that used different methods. Estimates reflect the marginal impact of HPV immunization in a population of women that is assumed will maintain historically high cervical cancer rates as they age. The estimates do not reflect either the costs or benefits of recommended HPV immunization for adolescent males. Benefits are limited to cervical cancer reduction. Although health benefits from preventing other HPV-associated diseases that are not included are likely to be small, the impacts on cost may be more substantial and might increase the CE score by one point. Expansion of the ACIP recommendation to all adults modestly increased health impact and reduced costeffectiveness. The increased uncertainty of the total score reflects uncertainty of the effectiveness of the vaccine in preventing mortality. Estimated benefits are limited to those who enroll in and complete an intensive intervention, typically of 6 to 12 months long. Costs include a substantial time cost for patients to participate in intensive intervention and out-of-pocket costs for physical activity and an improved diet. Therefore, the service would be more cost-effective from a medical payer's perspective that excludes these costs. The increased uncertainty of total score reflects potential for CE score to increase by 2 due to dense distribution of CE estimates among many services in the range. Estimated benefits are based on reduced HIV incidence among those who contract syphilis and reflect higher susceptibility to HIV among those with untreated syphilis. The impact on health from earlier identification and treatment of syphilis itself is not a a a Page 5 of 8

6 Vision, children Breast cancer Depression, adolescents Depression, adults Obesity, children and adolescents Pneumococcal immunization, adults Herpes zoster immunization Osteoporosis Screen children between ages 3 and 5 routinely to detect amblyopia. Biennial mammography for women aged years; prior to age 50 an individual decision. Screen adolescents ages for depression with systems to assure accurate diagnosis, treatment, and follow-up. Screen adults for depression with systems to assure accurate diagnosis, treatment, and follow-up. Screen children ages 6 and older for obesity. Offer or refer obese children to comprehensive, intensive behavioral intervention. Immunize adults aged 65+ against pneumococcal disease with PCV13 and PPSV23. Single dose of vaccine for adults 60 and older. Screen women ages 65 and older and younger women whose fracture risk is equal to or greater than that of 65-year-old included in the estimates. Screening pregnant women to prevent congenital syphilis is not addressed by this analysis. Substantial variation in plausible ranges for the benefits of earlier detection through rather than treating only with symptomatic presentation result in a wide range of possible CE ratios. Although a C grade recommendation from the USPSTF for women ages 40-49, we include biennial for this age group in our estimate because during this age range is covered under the Affordable Care Act and 70% of women currently elect to be screened. The increased uncertainty of the total score reflects based case estimates for both CPB and CE that are near the top of their scoring range. The increased uncertainty of the total score reflects the potential for both CPB and CE scores to change in the same direction in multivariate sensitivity analysis. Compared to in adolescents, a larger agerange produces greater overall health benefit, but a lower incidence rate combined with higher portion of cases recognized without reduces costeffectiveness. The increased uncertainty of the total score reflects the potential for both CPB and CE scores to change in the same direction in multivariate sensitivity analysis. Benefits reflect reduced adiposity-related diseases of adulthood. In the base case, we presume that 50% of children who enroll in and complete intensive intervention maintain the reduction in weight through adult years. Benefits do not include any impact independent of weight change on blood pressure, cholesterol or diabetes, such as those included in the adult intervention. Costs include a substantial time cost for parents to accompany children in intensive intervention and out-of-pocket costs for physical activity and improved diet. Therefore, the service would be more cost-effective from a medical payer's perspective that excludes these costs. Introduction of the PCV13 vaccine in the childhood immunization series had a substantial impact on disease incidence in older adults, reducing the impact of the adult pneumococcal vaccine compared to our prior estimates. Addition of the PCV13 vaccine for adults in 2014, while shown to be CE, also reduced the overall cost-effectiveness of pneumococcal vaccinations for older adults. The increased uncertainty of the total score reflects a wide plausible range of CE scores in multivariate sensitivity analysis. Introduction of generic alendronate did not substantially improve cost-effectiveness when assuming that just 10% of patients cannot tolerate generic alendronate and switch to much more expensive therapy a a a a a Page 6 of 8

7 Folic acid chemoprevention Meningococcal immunization Tdap/Td booster white women with no additional risk factors. Women planning or capable of pregnancy should take a daily supplement with 0.4 to 0.8 mg of folic acid. A single dose of quadrivalent vaccine recommended for year-olds, with a booster at age 16. One time Tdap and Td booster every 10 years. Estimates of greater-than-expected impact from the food fortification program introduced in 1998 resulted in a lower potential impact of folic acid supplements. Addition of one-time Tdap into the Td booster series, while shown to be cost-effective, did not substantially improve the CE of the series. a Sensitivity analysis indicated that a change of score of 2 or more is possible Table A2. Evolving Prevention Priorities: Previous scores for current rankings Service name (shortened) Significant changes to service Childhood immunization series Vaccines changed for each analysis. New evidence of larger Tobacco use, brief counseling to prevent a 10 8 effectiveness of counseling than initiation by children, adolescents modeled in Tobacco use and brief cessation intervention, adults Alcohol misuse and brief intervention Aspirin chemoprevention for those at Significant change to 8 10 N/A higher risk of CVD recommended target population. Cervical cancer Colorectal cancer Chlamydia and gonorrhea Gonorrhea added for 2016 ranking. Cholesterol Significant change in criteria for women. Hypertension AAA 6 N/A N/A Healthy diet counseling for those at higher risk of CVD 6 2 N/A HIV 6 N/A N/A HPV immunization 6 N/A N/A Influenza immunization, adults Obesity, adults 6 5 N/A Syphilis 6 N/A N/A Vision, children Significant change to recommended target population and evidence base expanded to include direct impact on blood pressure, lipids and diabetes. Was adults ages 50+ in 2006; was adults ages 65+ in Evidence base expanded to include direct impact on blood pressure, lipids and diabetes. Page 7 of 8

8 Breast cancer Younger women added. Depression, adolescents 5 N/A N/A Depression, adults 5 4 Recommendation no longer limited to primary care systems that already have systems in place to ensure follow-up. Obesity, children and teens 5 N/A N/A Pneumococcal immunization, adults Vaccination age previously 65+. Herpes zoster immunization 4 N/A N/A Osteoporosis 4 4 Introduction of generic alendronate. Folic acid chemoprevention National food fortification program reduced underlying risk. Meningococcal immunization 2 N/A N/A Tdap/Td booster a In 2003, the USPSTF concluded that the evidence was insufficient to recommend for or against routine for tobacco use or interventions to prevent and treat tobacco use and dependence in children or adolescents (I statement). That recommendation was in effect at the time of the 2006 rankings. Page 8 of 8